A comparison of the onset of action of salbutamol and formoterol in reversing methacholine-induced bronchoconstriction

This single-centre, randomized, double-blind, double-dummy four-way cross-over study in 24 moderately severe asthmatic patients compared the speed of onset of recommended doses of salbutamol (200 micrograms) and formoterol (12 micrograms) delivered by metered-dose inhaler in reversing the bronchoconstriction induced by a cumulative dose of methacholine to produce a 20% decrease (PD20) in forced expiratory volume in 1 s (FEV1). Specific airway conductance (SGAW) and airway resistance (RAW) were measured in baseline condition, immediately after challenge and 0.5, 1.5, 3, 5, 10, 15, 30, 60 min and every hour up to 4 h after inhalation of the trial drug. FEV1 was measured in baseline condition, after challenge and 15, 30 and 60 min and then every 30 min up to 4 h after inhalation of the study drug. The primary efficacy parameter was the change in SGAW. Salbutamol produced a two-fold increase in SGAW within 4 min and a maximum increase after 79.3 min. Formoterol produced a two-fold increase in SGAW after 5 min and a maximum increase after 119.6 min. Changes in SGAW were slightly, but consistently, higher during the first 2 h after inhalation of salbutamol, both in absolute values and as a percentage of the maximum response. Differences were significant at 10, 15 and 30 min time points. There was no significant difference between the maximum values of SGAW after the two drugs. Changes in RAW and FEV1 reflected the differences in SGAW. It was concluded that in methacholine-induced bronchoconstriction both formoterol and salbutamol have a very fast onset of action, achieving prechallenge values of SGAW within 3 min, salbutamol being slightly faster than formoterol.